Making migraine easier to stomach: the role of the gut−brain−immune axis in headache disorders

Background and Purpose

Headache disorders place a significant burden on the healthcare system, being the leading cause of disability in those under 50 years. Novel studies have interrogated the relationship between headache disorders and gastrointestinal dysfunction, suggesting a link between the gut−brain−immune (GBI) axis and headache pathogenesis. Although the exact mechanisms driving the complex relationship between the GBI axis and headache disorders remain unclear, there is a growing appreciation that a healthy and diverse microbiome is necessary for optimal brain health.

Methods

A literature search was performed through multiple reputable databases in search of Q1 journals within the field of headache disorders and gut microbiome research and were critically and appropriately evaluated to investigate and explore the following; the role of the GBI axis in dietary triggers of headache disorders and the evidence indicating that diet can be used to alleviate headache severity and frequency. The relationship between the GBI axis and post-traumatic headache is then synthesized. Finally, the scarcity of literature regarding paediatric headache disorders and the role that the GBI axis plays in mediating the relationship between sex hormones and headache disorders are highlighted.

Conclusions

There is potential for novel therapeutic targets for headache disorders if understanding of the GBI axis in their aetiology, pathogenesis and recovery is increased.     

Prospective cohort study of high-volume transanal irrigation in patients with constipation and/or faecal incontinence

Aim

The aim of this work was to determine the clinical efficacy of high-volume transanal irrigation (TAI) in patients with constipation and/or faecal incontinence using validated symptom and quality of life questionnaires.

Method

This was a prospective cohort study of 114 consecutive patients with constipation and/or faecal incontinence (Rome IV defined) who started TAI. A comprehensive questionnaire was completed at baseline and 4, 12, 26 and 52 weeks’ follow-up. The primary objective was significant symptom reduction [≥30%; Cleveland Clinic Constipation Score (CCCS) and St Marks Incontinence Score (SMIS)] in those who continued TAI at 52 weeks. Secondary objectives were (1) continuation rates of TAI, (2) effect on quality of life (QoL) and (3) identification of predictors for continuation.

Results

A total of 59 (51.8%) patients with constipation, 26 (22.8%) with faecal incontinence and 29 (25.4%) with coexistent symptoms were included. At 52 weeks, 41 (36.0%) patients continued TAI, 63 (55.2%) stopped and 10 (8.8%) patients were lost to follow-up. In those who continued TAI at 52 weeks (n = 41), no reduction of constipation symptoms was observed. Median Patient Assessment of Constipation Quality of Life scores decreased on most domains, indicating QoL improvement. Reduction of faecal incontinence occurred in 5/9 (55.6%) patients with faecal incontinence and in 3/10 (30.0%) patients with coexistent symptoms. The median SMIS per-individual decreased in patients with coexistent symptoms (2; interquartile range 0–4; p = 0.023). Median Fecal Incontinence Quality of Life scores increased in most domains, indicating improved QoL. No clinical characteristics predicted continuation.

Conclusion

One-third (n = 41) of patients continued TAI at 52 weeks. In those who continued TAI at 52 weeks, symptoms of faecal incontinence (SMIS) were reduced but not constipation (CCCS). QoL related to both constipation and faecal incontinence improved. No clinical characteristics predicted continuation.     

IGF2 and IGF1R identified as novel tip cell genes in primary microvascular endothelial cell monolayers

Tip cells, the leading cells of angiogenic sprouts, were identified in cultures of human umbilical vein endothelial cells (HUVECs) by using CD34 as a marker. Here, we show that tip cells are also present in primary human microvascular endothelial cells (hMVECs), a more relevant endothelial cell type for angiogenesis. By means of flow cytometry, immunocytochemistry, and qPCR, it is shown that endothelial cell cultures contain a dynamic population of CD34⁺ cells with many hallmarks of tip cells, including filopodia-like extensions, elevated mRNA levels of known tip cell genes, and responsiveness to stimulation with VEGF and inhibition by DLL4. Furthermore, we demonstrate that our in vitro tip cell model can be exploited to investigate cellular and molecular mechanisms in tip cells and to discover novel targets for anti-angiogenesis therapy in patients. Small interfering RNA (siRNA) was used to knockdown gene expression of the known tip cell genes angiopoietin 2 (ANGPT2) and tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1), which resulted in similar effects on tip cells and sprouting as compared to inhibition of tip cells in vivo. Finally, we identified two novel tip cell-specific genes in CD34⁺ tip cells in vitro: insulin-like growth factor 2 (IGF2) and IGF-1-receptor (IGF1R). Knockdown of these genes resulted in a significant decrease in the fraction of tip cells and in the extent of sprouting in vitro and in vivo. In conclusion, this study shows that by using our in vitro tip cell model, two novel essential tip cells genes are identified.     

Trends Across the Night in Patronage,Intoxication, and Licensed Venue Characteristics in Five Australian Cities

Background: While alcohol-related harm is reportedly greater on weekend evenings, research investigating trends in the intoxication levels of patrons and factors that increase risk of harm over the night is lacking. Objectives: The aim was to observe trends over the course of the night for patron demographics, venue characteristics and patron intoxication. Methods: Observations of licensed venues and patrons in night-time entertainment districts of five Australian cities were conducted. In total, 798 observations occurred between 9 pm and 2 am on Friday and Saturday nights across 61 unique bars, nightclubs, and pubs. Patron characteristics such as gender and percentage of patrons under 25 years of age were estimated. Measures of venue characteristics included number of patrons, percentage venue capacity, ease of patron movement, bar crowding, and time to service. Measures of intoxication included the percentage of patrons showing any signs of alcohol intoxication, percentage of patrons too intoxicated to remain in the venue, overall level of intoxication, and percentage of patrons showing signs of drug use. Results: Patron capacity increased across the night, peaking at 11 pm in bars, and 1 am in nightclubs. Patron intoxication measures increased for all venue types across the night. Patrons showed more signs of drug use in nightclubs than other venue types. Conclusions: Increasing intoxication and decreasing patron numbers later in the night provides support for restricted trading hours and improved responsible service of alcohol policies. Specific venue types should be targeted to reduce drug use in the night-time economy.     

Nutrition as a Vehicle for Cardiovascular Translational Research

It is becoming increasingly evident that poor nutrition plays an important role in inducing cardiovascular disease. Just as importantly, data now support the contention that appropriate nutritional interventions may have just as important an effect in preventing or delaying the appearance of cardiovascular disease. If this is indeed true, then it is critical that these advances in our knowledge of the effects of nutritional interventions be translated into effective strategies to combat cardiovascular disease. It is argued in this paper, with a few specific examples, that the translation of nutritional interventions can provide powerful approaches to alleviating the clinical challenges currently facing us today in the cardiovascular field. Furthermore, the value-added economic advantages of translating nutritional strategies on a wide scale into the public become another intriguing argument to further support investigations in this growing field.     

UpStart Parent Survey: A New Psychometrically Valid Tool for the Evaluation of Prevention-focused Parenting Programs

Parents are the most significant influence on the growth and development of young children. All parents can increase their knowledge of developmental milestones and parenting practices by participating in effective programs that offer information and support. However, there is limited outcome evaluation of programs offering these services. Prevention-focused parenting programs (P-FPPs) are key frontline services designed to educate parents and improve the overall well-being of children. Evaluation of these programs is currently weak; this is not to say they are ineffective, rather that their effectiveness has been poorly evaluated. Rigorous evaluation of P-FPPs would support informed funding and evidence-based policy decisions. The purpose of this study was to conduct a preliminary psychometric analysis of the UpStart Parent Survey (USPS)—a tool developed specifically for evaluating this type of program. Preliminary analysis revealed uni-dimensionality of each scale, strong internal consistency and temporal stability, as well as strong concurrent validity on 9 of the 11 items examined with an urban Canadian population. In its first round of psychometric evaluation, the USPS demonstrated promise as a brief, easy to administer, scientifically rigorous tool for the evaluation of prevention-focused parenting programs.     

Rural Residence and Hispanic Ethnicity: Doubly Disadvantaged for Diabetes?

CONTEXT: Hispanics are at increased risk for diabetes, while rural residents have historically had decreased access to care. PURPOSE: To determine whether living in a rural area and being Hispanic confers special risks for diagnosis and control of diabetes. METHODS: We analyzed the Third National Health and Nutrition Examination Survey (1988-1994). Hispanics and non-Hispanic white adults were classified according to rural/urban residence to create 4 ethnicity-residence groups. Investigated outcomes were previously diagnosed and undiagnosed diabetes. Among those with diagnosed diabetes, we investigated control of glucose, hypertension, and lipids. FINDINGS: The prevalence of diagnosed diabetes was greatest for rural residents, especially for rural Hispanics (8.2%) versus that for urban whites (4.6%), rural whites (6.5%), or urban Hispanics (4.5%), (P < .01). However, urban Hispanics were most likely to have undiagnosed diabetes at 3.7%, versus 2.3% of rural whites, 2.8% of urban whites, and 2.7% of rural Hispanics (P = .04). Among people with diagnosed diabetes, there was no difference in glycemic control between the 4 groups. Rural Hispanics with diagnosed diabetes had the greatest prevalence of elevated systolic blood pressure at 45%, compared to 37% of urban whites, 29% of rural whites, 28% of urban Hispanics (P = .01). In regression models controlling for potential confounders, there were no differences among urban and rural whites and Hispanics in the likelihood of undiagnosed diabetes or in glycemic control for those with diagnosed diabetes. CONCLUSIONS: Initiatives that target Hispanic health, and especially diabetes, should acknowledge rural/urban Hispanic health differences.     

Ultrastructural spectrum of medulloblastoma with immunocytochemical correlations

Electron microscopy was used to examine 72 cases of medulloblastoma to better characterize the ultrastructural spectrum of this tumor. Twenty-four cases showed prominent neural differentiation. Twenty-three cases showed minimal (21) or no (2) recognizable neural differentiation, and the remainder of the cases (25) showed intermediate differentiation. All 42 cases tested stained for neuron-specific enolase, 28 for synaptophysin, and 12 for neurofilament protein. All cases showed strong reactivity for glial fibrillary acidic protein (GFAP) within reactive astrocytes. Three cases showed reactivity for GFAP within tumor cells. Medulloblastoma exhibits a broad spectrum of neural differentiation, with nearly all cases showing at least some degree of this change, and it universally exhibits participation of reactive astrocytes which can create a potential for diagnostic confusion.